Positive results have been reported from two replicate pivotal phase 3 trials evaluating the efficacy and safety of elagolix (AbbVie/Neurocrine Biosciences) in premenopausal women with endometriosis. The data demonstrated that, compared with placebo at three and six months, patients treated with elagolix reported statistically significant reductions in scores for dysmenorrhea (DYS) and nonmenstrual pelvic pain (NMPP) associated with endometriosis, as measured by the Daily Assessment of Endometriosis Pain scale.
The first pivotal trial was a 24-week, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of elagolix (150 mg once daily or 200 mg twice daily) in 872 women 18 to 49 years of age with moderate-to-severe endometriosis-associated pain. The study was conducted at 175 sites in the United States, Puerto Rico, and Canada. An extension study permitted some women to be treated for an additional six months.
The second pivotal trial employed the same design as the first study and included 815 women with moderate-to-severe endometriosis-associated pain in 13 countries (including the U.S.). As in the first trial, an extension study permitted some women to be treated for an additional six months.
Together, these two pivotal studies evaluated the safety and efficacy of elagolix in nearly 1,700 women with moderate-to-severe endometriosis-associated pain, representing the largest prospective randomized endometriosis trials conducted to date.
In the two studies, both dosages of elagolix demonstrated a statistically significant (P < 0.001) improvement compared with placebo in the percentage of DYS and NMPP responders. In the first study, at three months, 46% of patients treated with 150 mg once daily and 76% treated with 200 mg twice daily of elagolix were classified as DYS responders compared with 20% of patients in the placebo group. Fifty percent of patients treated with 150 mg once daily and 55% of those treated with 200 mg twice daily of elagolix were classified as NMPP responders compared with 36% of patients in the placebo group. The second pivotal study demonstrated similar results.
The safety profile of elagolix was consistent across both studies. In the first study, the most common adverse events (AEs) during six months of treatment included hot flush (7%, 24%, 42% for placebo, 150 mg once daily, and 200 mg twice daily, respectively), headache (10%, 15%, and 17%), and nausea (14%, 10%, and 16%). Discontinuation rates due to AEs were 5.9% and 6.1% for placebo in study 1 and study 2, respectively; 6.4% and 4.4% for 150 mg once daily in study 1 and study 2, respectively; and 9.0% and 10.0% for 200 mg twice daily in study 1 and study 2, respectively.
Elagolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, is an orally administered, short-acting molecule that blocks endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland. Administration of the medication results in rapid, reversible, dose-dependent inhibition of luteinizing hormone and follicle-stimulating hormone (FSH) secretion, leading to reduced ovarian production of the sex hormones estradiol and progesterone during therapy. Elagolix is being investigated in diseases that are mediated by sex hormones, such as uterine fibroids and endometriosis. To date, the medication has been studied in more than 40 clinical trials involving more than 3,000 subjects. Phase 3 trials of elagolix for the management of uterine fibroids are ongoing.
Source: AbbVie; October 19, 2016.